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      Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity?

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          Abstract

          Background:

          Viral infectivity depends on interactions between components of the host cell plasma membrane and the virus envelope. Here we review strategies that could help stem the advance of the SARS-COV-2 epidemic.

          Methods and Results:

          We focus on the role of lipid structures, such as lipid rafts and cholesterol, involved in the process, mediated by endocytosis, by which viruses attach to and infect cells. Previous studies have shown that many naturally derived substances, such as cyclodextrin and sterols, could reduce the infectivity of many types of viruses, including the coronavirus family, through interference with lipid-dependent attachment to human host cells.

          Conclusions:

          Certain molecules prove able to reduce the infectivity of some coronaviruses, possibly by inhibiting viral lipid-dependent attachment to host cells. More research into these molecules and methods would be worthwhile as it could provide insights the mechanism of transmission of SARS-COV-2 and, into how they could become a basis for new antiviral strategies.

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          Most cited references26

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          Use of cyclodextrins to manipulate plasma membrane cholesterol content: evidence, misconceptions and control strategies.

          The physiological importance of cholesterol in the cell plasma membrane has attracted increased attention in recent years. Consequently, the use of methods of controlled manipulation of membrane cholesterol content has also increased sharply, especially as a method of studying putative cholesterol-enriched cell membrane domains (rafts). The most common means of modifying the cholesterol content of cell membranes is the incubation of cells or model membranes with cyclodextrins, a family of compounds, which, due to the presence of relatively hydrophobic cavity, can be used to extract cholesterol from cell membranes. However, the mechanism of this activity of cyclodextrins is not completely established. Moreover, under conditions commonly used for cholesterol extraction, cyclodextrins may remove cholesterol from both raft and non-raft domains of the membrane as well as alter the distribution of cholesterol between plasma and intracellular membranes. In addition, other hydrophobic molecules such as phospholipids may also be extracted from the membranes by cyclodextrins. We review the evidence for the specific and non-specific effects of cyclodextrins and what is known about the mechanisms for cyclodextrin-induced cholesterol and phospholipid extraction. Finally, we discuss useful control strategies that may help to verify that the observed effects are due specifically to cyclodextrin-induced changes in cellular cholesterol.
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            COVID-19 (Novel Coronavirus 2019) - recent trends.

            The World Health Organization (WHO) has issued a warning that, although the 2019 novel coronavirus (COVID-19) from Wuhan City (China), is not pandemic, it should be contained to prevent the global spread. The COVID-19 virus was known earlier as 2019-nCoV. As of 12 February 2020, WHO reported 45,171 cases and 1115 deaths related to COVID-19. COVID-19 is similar to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) virus in its pathogenicity, clinical spectrum, and epidemiology. Comparison of the genome sequences of COVID-19, SARS-CoV, and Middle East Respiratory Syndrome coronavirus (MERS-CoV) showed that COVID-19 has a better sequence identity with SARS-CoV compared to MERS CoV. However, the amino acid sequence of COVID-19 differs from other coronaviruses specifically in the regions of 1ab polyprotein and surface glycoprotein or S-protein. Although several animals have been speculated to be a reservoir for COVID-19, no animal reservoir has been already confirmed. COVID-19 causes COVID-19 disease that has similar symptoms as SARS-CoV. Studies suggest that the human receptor for COVID-19 may be angiotensin-converting enzyme 2 (ACE2) receptor similar to that of SARS-CoV. The nucleocapsid (N) protein of COVID-19 has nearly 90% amino acid sequence identity with SARS-CoV. The N protein antibodies of SARS-CoV may cross react with COVID-19 but may not provide cross-immunity. In a similar fashion to SARS-CoV, the N protein of COVID-19 may play an important role in suppressing the RNA interference (RNAi) to overcome the host defense. This mini-review aims at investigating the most recent trend of COVID-19.
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              Multifaceted roles for lipids in viral infection

              Viruses have evolved complex and dynamic interactions with their host cell. In recent years we have gained insight into the expanding roles for host lipids in the virus life cycle. In particular, viruses target lipid signaling, synthesis, and metabolism to remodel their host cells into an optimal environment for their replication. This review highlights examples from different viruses that illustrate the importance of these diverse virus–lipid interactions.
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                Author and article information

                Journal
                Acta Biomed
                Acta Biomed
                Acta Bio Medica : Atenei Parmensis
                Mattioli 1885 (Italy )
                0392-4203
                2531-6745
                2020
                19 March 2020
                : 91
                : 1
                : 161-164
                Affiliations
                [1 ]MAGI-Euregio, Bolzano, Italy
                [2 ] Department of Anaesthesia and Intensive Care, Fondazione Poliambulanza, Brescia, Italy
                [3 ] Department of Pharmaceutical Sciences, University of Perugia, Via Fabretti 48, 06123 Perugia, Italy
                [4 ] Institute of Genomic Medicine, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy
                [5 ] Pathology Division of Anatomic Pathology Dept. of Surgical and Diagnostic Sciences (DISC) University of Genova, Italy
                [6 ] UOSD Fetal Pathology and Ginecology IRCCS. Istituto Giannina Gaslini, Genova, Italy
                [7 ] Institute G. Gaslini, Children’s Hospital, Genova, Italy
                [8 ] Department of Vascular Rehabilitation, San Giovanni Battista Hospital, Rome, Italy
                [9 ] Pharmacy Fiorentini, Brescia, Italy
                [10 ] Human Nutrition Research Center, Sacro Cuore Catholic University, Rome, Italy
                [11 ] Department of Chemistry, Biology and Biotechnology, University of Perugia, Perugia, Italy
                [12 ] Department of Surgery, Fondazione Poliambulanza, Brescia, Italy
                [13 ] EBTNA-Lab, Rovereto (TN), Italy
                Author notes
                Correspondence: Mirko Baglivo MAGI Euregio, Via Maso della Pieve, 60/A, 39100 Bolzano (BZ) Italy E-mail: mirko.baglivo@ 123456assomagi.org
                Article
                ACTA-91-161
                10.23750/abm.v91i1.9402
                7569585
                32191676
                886f2587-d943-4822-8850-4e56cac853e7
                Copyright: © 2020 ACTA BIO MEDICA SOCIETY OF MEDICINE AND NATURAL SCIENCES OF PARMA

                This work is licensed under a Creative Commons Attribution 4.0 International License

                History
                : 11 March 2020
                : 18 March 2020
                Categories
                New Frontiers

                coronavirus,sars-cov-2,lipid raft,cholesterol,phytosterol
                coronavirus, sars-cov-2, lipid raft, cholesterol, phytosterol

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